title: Significance of thrombomodulin release from gingival epithelial cells in periodontitis patients.
abstract: OBJECTIVE
  Thrombomodulin, a cell transmembrane glycoprotein, binds to thrombin and converts it from a procoagulant protease to an anticoagulant enzyme that activates protein C. Thrombomodulin is very important in regulating the function of thrombin. Elevated soluble thrombomodulin is present in the gingival crevicular fluid of subjects with periodontitis. The objective of the present study was to investigate the mechanisms about the elevated soluble thrombomodulin in gingival crevicular fluid.
  
  
  METHODS
  Gingival sections from six patients with chronic periodontitis and from three periodontally healthy subjects were immunostained for thrombomodulin detection. Thrombomodulin levels were investigated in the gingival crevicular fluid of 11 subjects with chronic periodontitis. The effects of neutrophil enzymes on thrombomodulin release and on thrombomodulin in the gingival crevicular fluid were examined by an enzyme-linked immunosorbent assay or by Western blotting.
  
  
  RESULTS
  The expression of gingival epithelial thrombomodulin was lost or decrease near infiltrating neutrophils. Thrombomodulin was rapidly released from gingival epithelial cells by neutrophil enzymes, and gingival crevicular fluid with periodontitis included the proteolytic cleavage thrombomodulin using immunoblotting analysis. The thrombomodulin release was not caused by rapid cell damage, on lactate dehydrogenase assay. There were significant differences in thrombomodulin content between gingival crevicular fluid samples from healthy and diseased sites, regardless of the degree of probing depth.
  
  
  CONCLUSIONS
  Neutrophil enzymes induced rapid thrombomodulin release from the membrane surface of gingival epithelial cells. This might explain the thrombomodulin increase in gingival crevicular fluid with local diseased gingiva. Elevation of thrombomodulin in gingival crevicular fluid may be a potential marker of epithelial cell membrane injury.
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan. takashi@dentb.hal.kagoshima-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Matsuyama
authors.forename: M
authors.initials: M
authors.lastname: Tokuda
authors.forename: Y
authors.initials: Y
authors.lastname: Izumi
mesh_terms: D016301:Alveolar Bone Loss / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D056649:Cathepsin G; D002403:Cathepsins / Q000032:analysis; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005881:Gingiva / Q000378:metabolism / Q000473:pathology*; D005883:Gingival Crevicular Fluid / Q000737:chemistry*; D005884:Gingival Hemorrhage / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D019272:Leukocyte Elastase / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D010514:Periodontal Pocket / Q000378:metabolism / Q000473:pathology; D010518:Periodontitis / Q000378:metabolism / Q000473:pathology*; D012697:Serine Endopeptidases / Q000032:analysis; D015842:Serine Proteinase Inhibitors; D018180:Thrombomodulin / Q000032:analysis* / Q000378:metabolism; D000515:alpha 1-Antitrypsin
chemical_list: D015842:Serine Proteinase Inhibitors; D018180:Thrombomodulin; D000515:alpha 1-Antitrypsin; D007770:L-Lactate Dehydrogenase; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase